Diffuse Large B-Cell Lymphoma with High Risk of Central Nervous System Damage: A Literature Review, Prevention, Treatment, and Prognosis

Abstract

AIM. To assess the feasibility of preventing the CNS damage in intermediate/high risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) in accordance with CNS-IPI criteria.

MATERIALS & METHODS. The trial was based on the clinical data from 60 patients with newly diagnosed DLBCL treated at the NN Blokhin National Medical Cancer Research Center from 2018 to 2024. The patients were 29–80 years of age (median 59 years); there were 34 women and 26 men. In accordance with the immunohistochemical algorithm of C.P. Hans, GCB subtype of DLBCL was identified in 18 (30 %) patients, non-GCB subtype was detected in 35 (58 %), and in 7 (12 %) patients subtype was not specified. By the time of primary DLBCL diagnosis, in 58 out of 60 patients tumor stage 4 was found, in 56 patients LDH increase was reported, and 22 patients showed ECOG ≥ 2. Extranodal lesions (> 1 zone) were identified in 53/60 patients. In accordance with the CNS-IPI score, with respect to CNS damage there were 22 (37 %) intermediate and 36 (60 %) high risk patients. In first-line therapy, R-CHOP (n = 40; 67 %) was most commonly used, R-DA-EPOCH (n = 10; 17 %) and Pola-R-CHP (n = 7; 11 %) were administered less often; 3 patients (5 %) received R-B. In 18 (30 %) patients, the initial lesions were treated with radiotherapy after completing drug chemotherapy. Different variants of CNS damage prevention in DLBCL included intrathecal (IT) administration of 3 drugs (methotrexate, cytarabine, and dexamethasone) and/or 2 methotrexate (МТХ) 3–3,5 g/m² infusions. The trial identified two clinically comparable groups of DLBCL patients with CNS-IPI intermediate/high risk of CNS damage, who received chemotherapy throughout different periods of time (2018–2021 and 2022–2024). During the first period (n = 30), to prevent possible CNS damage, both methods were used as monotherapy or combined regimens consecutively. МТХ IT + МТХ HD (high dose) as prevention was administered to 20 (67 %) patients, 2 (7 %) patients received only МТХ HD, and 8 (26 %) patients received only МТХ IT. In the second group, CNS damage prevention was not provided for this category of DLBCL patients.

RESULTS. In the total group (n = 60), with the follow-up median of 24 months, the 2-year progression-free survival (PFS) was 76 % (median 44 months), whereas the 2-year overall survival (OS) was 87 % (median 49 months). Age > 60 years was associated with the worst rate of the 2-year PFS (72 %) compared with patients ≤ 60 years (90 %) (p = 0.04). Besides, the 2-year OS in women was 77 % and 100 % in men, whereas in the groups of patients with ECOG ≥ 2 vs. < 2 it was 63 % and 95 %, respectively (p = 0.04). In patients with prevention of CNS damage, the 2-year PFS was 95 % vs. 64 % in patients without it (p = 0.001), and the 2-year OS in them was 95 % and 77 %, respectively (p = 0.05). In the course of this trial, the rate of DLBCL relapses with CNS involvement was 5 % (n = 3). Relapses were detected in 6, 18, and 46 months from the beginning of chemotherapy. CNS damage prevention was not performed in 3 patients with relapses.

CONCLUSION. The data obtained in this ambispective trial support systemic and intrathecal use of methotrexate to increase the overall PFS rate and to reduce the relapse rate, also in CNS. The methods of CNS damage prevention are not associated with additional toxicity in DLBCL patients with intermediate/high CNS-IPI risk score.